Origin and evolution of the archaeo-eukaryotic primase superfamily andrelated palm-domain proteins: structural insights and new members.

Nucleic Acids Res. 2005; 33: 3875-96

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We report an in-depth computational study of the protein sequences andstructures of the superfamily of archaeo-eukaryotic primases (AEPs). Thisanalysis greatly expands the range of diversity of the AEPs and revealsthe unique active site shared by all members of this superfamily. Inparticular, it is shown that eukaryotic nucleo-cytoplasmic large DNAviruses, including poxviruses, asfarviruses, iridoviruses, phycodnavirusesand the mimivirus, encode AEPs of a distinct family, which also includesthe herpesvirus primases whose relationship to AEPs has not beenrecognized previously. Many eukaryotic genomes, including chordates andplants, encode previously uncharacterized homologs of these predictedviral primases, which might be involved in novel DNA repair pathways. At adeeper level of evolutionary connections, structural comparisons indicatethat AEPs, the nucleases involved in the initiation of rolling circlereplication in plasmids and viruses, and origin-binding domains ofpapilloma and polyoma viruses evolved from a common ancestral protein thatmight have been involved in a protein-priming mechanism of initiation ofDNA replication. Contextual analysis of multidomain protein architecturesand gene neighborhoods in prokaryotes and viruses reveals remarkableparallels between AEPs and the unrelated DnaG-type primases, inparticular, tight associations with the same repertoire of helicases.These observations point to a functional equivalence of the two classes ofprimases, which seem to have repeatedly displaced each other in variousextrachromosomal replicons.